Oxidation Under Reductive Conditions: From Benzylic Ethers to Acetals with Perfect Atom‐Economy by Titanocene(III) Catalysis

Abstract

Described here is atitanocene-catalyzed reaction for the synthesis of acetals and hemiaminals from benzylic ethers and benzylic amines,r espectively,with pendant epoxides.T he reaction proceeds by catalysis in single-electron steps.T he oxidative addition comprises an epoxide opening.AnH-atom transfer,t og enerate ab enzylic radical, serves as ar adical translocation step,a nd an organometallic oxygen rebound as ar eductive elimination. The reaction mechanism was studied by high-level dispersion corrected hybrid functional DFT with implicit solvation. The low-energy conformational space was searched by the efficient CREST program. The stereoselectivity was deduced from the lowest lying benzylic radical structures and their conformations are controlled by hyperconjugative interactions and steric interactions between the titanocene catalyst and the aryl groups of the substrate.A ni nteresting mechanistic aspect is that the oxidation of the benzylic center occurs under reducing conditions. Scheme 1. Atom-economic transformation of benzylic ethers into acetals by titanocene(III) catalysis in single-electrons teps (SET).

Photoredox/Ti Dual‐Catalyzed Dehydroxylation of Cyclobutanone Oximes for γ‐Cyanoalkyl Radical Generation: Access to Cyanoalkyl‐Substituted Oxoindolines

“…The investigation of photocatalysts suggested other organic fluorophores such as 4CzIPN, 4DPAIPN, and 5CzBN resulted in inferior yields of 3 aa (entries 2–4). Ti catalysts with either different counterions (Cp 2 TiBr 2 , Cp 2 Ti(OTf) 2 , Cp 2 Ti(OMs) 2 , and Cp 2 Ti(TFA) 2 ) [21e,g] or different ligands (Cp*TiCl 3 and Ti(O i ‐Pr) 4 ) afforded 3 aa in lower yields than Cp 2 TiCl 2 (entries 5–10). Reactions in THF and DMF did not work so well as that in DCE (entries 11 and 12).…”

Reverse Regioselectivity in Reductive Ring Opening of Epoxide Enabled by Zirconocene and Photoredox Catalysis

“…Interestingly, ring opening of dibenzyl ether 1AG produced alcohol 2AG along with benzylidene acetal 4AG obtained in the previous titanocene-mediated ring opening via 1,5-hydrogen atom transfer (HAT). 36 In addition to trisubstituted epoxides (1AH-1AJ), natural product-derived epoxides (1AK-1AN) could also be readily opened in good yields. Comparisons to the analogous precedents performed by titanocene highlighted the reverse reactivity in ring opening.…”

“…DFT calculations indicated that ring opening with titanocene was endothermic, which is consistent with a previous study. 36 Since titanocene-bounded tertiary radical IIb is more stable than the corresponding primary radical IIa by 6.82 kcal/mol, ring opening under thermodynamic control results in a large abundance of IIb which undergoes HAT to afford IIIb as a major product. In contrast, ring opening with zirconocene was found to be extremely exothermic and practically irreversible.…”